WO2011127465A3 - Ship inhibitors and uses thereof - Google Patents

Ship inhibitors and uses thereof Download PDF

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Publication number
WO2011127465A3
WO2011127465A3 PCT/US2011/031930 US2011031930W WO2011127465A3 WO 2011127465 A3 WO2011127465 A3 WO 2011127465A3 US 2011031930 W US2011031930 W US 2011031930W WO 2011127465 A3 WO2011127465 A3 WO 2011127465A3
Authority
WO
WIPO (PCT)
Prior art keywords
subject
treating
inhibiting
cell
ship1
Prior art date
Application number
PCT/US2011/031930
Other languages
French (fr)
Other versions
WO2011127465A2 (en
Inventor
William G. Kerr
John D. Chisholm
Original Assignee
The Research Foundation Of The State University Of New York
Syracuse University Technology Transfer And Industrial Development Office
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by The Research Foundation Of The State University Of New York, Syracuse University Technology Transfer And Industrial Development Office filed Critical The Research Foundation Of The State University Of New York
Priority to EP11766857.4A priority Critical patent/EP2556055B1/en
Priority to ES11766857T priority patent/ES2742213T3/en
Priority to US13/640,162 priority patent/US9447139B2/en
Priority to EP19189158.9A priority patent/EP3581563B1/en
Priority to DK11766857.4T priority patent/DK2556055T3/en
Publication of WO2011127465A2 publication Critical patent/WO2011127465A2/en
Publication of WO2011127465A3 publication Critical patent/WO2011127465A3/en
Priority to US15/269,209 priority patent/US11319336B2/en
Priority to US17/542,090 priority patent/US20220162254A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
    • C07J1/0003—Androstane derivatives
    • C07J1/0007—Androstane derivatives not substituted in position 17
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
    • C07J1/0003—Androstane derivatives
    • C07J1/0011—Androstane derivatives substituted in position 17 by a keto group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
    • C07J31/003—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring the S atom directly linked to a ring carbon atom of the cyclopenta(a)hydrophenanthrene skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
    • C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
    • C07J41/0011—Unsubstituted amino radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of only two carbon atoms, e.g. pregnane derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
    • C07J41/0027—Azides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The present invention relates to SHIP inhibitor compounds and methods for using these compounds. In particular, the present invention discloses the following methods: (i) a method of treating graft versus host disease in a subject; (ii) a method of inhibiting a SHIP1 protein in a cell; (iii) a method of selectively inhibiting a SHIP1 protein in a cell; (iv) a method for treating or preventing graft-versus-host disease (GVHD) in a recipient of an organ or tissue transplant; (v) a method of modulating SHIP activity in a cell expressing SHIP1 or SHIP2; (vi) a method of ex vivo or in vitro treatment of transplants; (vii) a method of inhibiting tumor growth and metastasis in a subject; (viii) a method of treating a hematologic malignancy in a subject; (ix) a method of inducing apoptosis of multiple myeloma cells; (x) a method of treating multiple myeloma in a subject; (xi) a method of inhibiting the proliferation of a human breast cancer cell; and (xii) a method of treating breast cancer in a subject.
PCT/US2011/031930 2010-04-09 2011-04-11 Ship inhibitors and uses thereof WO2011127465A2 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
EP11766857.4A EP2556055B1 (en) 2010-04-09 2011-04-11 Ship inhibitors and uses thereof
ES11766857T ES2742213T3 (en) 2010-04-09 2011-04-11 SHIP inhibitors and their use
US13/640,162 US9447139B2 (en) 2010-04-09 2011-04-11 Ship inhibitors and uses thereof
EP19189158.9A EP3581563B1 (en) 2010-04-09 2011-04-11 Ship inhibitors and uses thereof
DK11766857.4T DK2556055T3 (en) 2010-04-09 2011-04-11 SHIP INHIBITORS AND APPLICATIONS THEREOF
US15/269,209 US11319336B2 (en) 2010-04-09 2016-09-19 Ship inhibitors and uses thereof
US17/542,090 US20220162254A1 (en) 2010-04-09 2021-12-03 Ship inhibitors and uses thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US32237810P 2010-04-09 2010-04-09
US61/322,378 2010-04-09

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US13/640,162 A-371-Of-International US9447139B2 (en) 2010-04-09 2011-04-11 Ship inhibitors and uses thereof
US15/269,209 Division US11319336B2 (en) 2010-04-09 2016-09-19 Ship inhibitors and uses thereof

Publications (2)

Publication Number Publication Date
WO2011127465A2 WO2011127465A2 (en) 2011-10-13
WO2011127465A3 true WO2011127465A3 (en) 2012-03-15

Family

ID=44763588

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2011/031930 WO2011127465A2 (en) 2010-04-09 2011-04-11 Ship inhibitors and uses thereof

Country Status (5)

Country Link
US (3) US9447139B2 (en)
EP (2) EP2556055B1 (en)
DK (1) DK2556055T3 (en)
ES (1) ES2742213T3 (en)
WO (1) WO2011127465A2 (en)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2742213T3 (en) 2010-04-09 2020-02-13 The Research Foundation Of The State Univ Of New York SHIP inhibitors and their use
CN104072564B (en) * 2013-03-28 2016-08-17 广州市赛普特医药科技股份有限公司 2 β, 3 α, 5 α-trihydroxy-androstane-6-ketone and preparation method thereof and purposes
EP3016660B1 (en) * 2013-07-01 2020-06-10 The Research Foundation for the State University of New York Ship inhibition to combat obesity
CA2986354A1 (en) * 2014-06-17 2015-12-30 The Research Foundation For The State University Of New York Ship inhibition to induce expression of granulocyte colony stimulating factor in a subject
US10736877B2 (en) 2015-12-31 2020-08-11 Syracuse University Tryptamine-based ship inhibitors for the treatment of cancer
WO2018093856A1 (en) 2016-11-16 2018-05-24 Gupte Sachin A Inhibitors of glucose-6-phosphate dehydrogenase for treating cardiovascular and pulmonary conditions
WO2019234189A1 (en) * 2018-06-06 2019-12-12 Centro Nacional De Investigaciones Cardiovasculares Carlos Iii (F.S.P.) Enhanced trained immunity in myeloid cells by ship-1 inhibition
US20220023315A1 (en) * 2018-07-31 2022-01-27 The Research Foundation For The State University Of New York Methods of activating microglial cells
CN112315964B (en) * 2020-12-07 2024-01-26 中国医科大学附属盛京医院 Application of cyclopentyl phenanthridine benzene compound in preparation of TLN1 protein inhibitor
CN114716499B (en) * 2022-04-24 2023-05-23 浙江工商大学 Biological sterol guanidyl modified cholic acid chelating agent, preparation method and application

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB900572A (en) * 1957-09-27 1962-07-11 Oletta S A Funtumia alkaloids
BE702699A (en) * 1967-08-16 1968-01-15
WO2008068037A1 (en) * 2006-12-08 2008-06-12 Jado Technologies Gmbh Cholesterylamines for the treatment and prevention of infectious diseases
WO2010045199A2 (en) * 2008-10-13 2010-04-22 University Of South Florida Method of modulating ship activity

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1000410A (en) * 1962-03-30 1965-08-04 Sterling Drug Inc Amino-androstanes
CS126738B5 (en) * 1965-08-31 1968-03-15
AU746878B2 (en) 1996-12-20 2002-05-02 Novo Nordisk A/S Meiosis regulating compounds
AU2003284140A1 (en) 2002-10-11 2004-05-04 Isis Pharmaceuticals, Inc. Method for inhibiting angiogenesis with ship-1 inhibitors
BRPI0408240A (en) 2003-03-11 2006-03-01 Trophos compound, use of a compound and pharmaceutical composition
CA2571440A1 (en) 2004-06-29 2006-01-12 Jadolabs Gmbh Use of steroid-derived pharmaceutical compositions for treating disorders relating to pathological processes in lipid rafts
EP2507221A1 (en) 2009-12-04 2012-10-10 Aquinox Pharmaceuticals Inc. Ship1 modulators and methods related thereto
ES2742213T3 (en) 2010-04-09 2020-02-13 The Research Foundation Of The State Univ Of New York SHIP inhibitors and their use
EP3016660B1 (en) 2013-07-01 2020-06-10 The Research Foundation for the State University of New York Ship inhibition to combat obesity

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB900572A (en) * 1957-09-27 1962-07-11 Oletta S A Funtumia alkaloids
BE702699A (en) * 1967-08-16 1968-01-15
WO2008068037A1 (en) * 2006-12-08 2008-06-12 Jado Technologies Gmbh Cholesterylamines for the treatment and prevention of infectious diseases
WO2010045199A2 (en) * 2008-10-13 2010-04-22 University Of South Florida Method of modulating ship activity

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
NIKOLAROPOULOS, SOTIRIOS ET AL.: "Formation of Acetamido-Aza-Steroids", J. HETEROCYCLIC CHEM., vol. 27, 1990, pages 1997 - 1999, XP055093508 *
PHILLIPPS, G. H. ET AL.: "A New Series of Steroidal Antidysrhythmic Agents", J. STEROID BIOCHEM., vol. 19, no. 1, 1983, pages 759 - 765, XP023413589 *
SYHORA, K. ET AL.: "Olefin-forming Elimination of the Amino Group", TETRAHEDRON LETT., vol. 28, 1965, pages 2369 - 2376, XP055093548 *

Also Published As

Publication number Publication date
US11319336B2 (en) 2022-05-03
WO2011127465A2 (en) 2011-10-13
EP2556055B1 (en) 2019-07-31
EP3581563A1 (en) 2019-12-18
EP3581563B1 (en) 2023-06-28
US20130102577A1 (en) 2013-04-25
DK2556055T3 (en) 2019-08-19
US20220162254A1 (en) 2022-05-26
US20170051006A1 (en) 2017-02-23
US9447139B2 (en) 2016-09-20
EP3581563C0 (en) 2023-06-28
EP2556055A4 (en) 2014-02-19
EP2556055A2 (en) 2013-02-13
ES2742213T3 (en) 2020-02-13

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